Bone matters: Ga-68 PSMA PET/CT volumetrics predict PSA-PFS and OS in bone-dominant mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-617.

[INTRODUCTION] This study aimed to evaluate the prognostic value of baseline, interim, and change-based (Δ) volumetric parameters derived from PSMA PET/CT imaging in predicting PSA progression-free survival (PSA-PFS) and overall survival (OS) in bone-dominant metastatic castration-resistant prostate cancer (mCRPC) patients treated with [¹⁷⁷Lu]Lu-PSMA-617.

[METHODS] This retrospective study included 56 bone-dominant mCRPC patients who underwent [⁶⁸Ga]Ga-PSMA PET/CT imaging before and after two cycles of [¹⁷⁷Lu]Lu-PSMA therapy. Quantitative parameters, including SUVmean, PSMA tumor volume (PSMA-TV), and total lesion PSMA activity (TL-PSMA), were extracted using a fixed threshold of SUV ≥ 3. Δ values were calculated as the relative change between baseline and interim scans. Associations with PSA-PFS and OS were analyzed using Cox regression and Kaplan-Meier survival analyses.

[RESULTS] The presence of new lesions on interim PSMA PET/CT and a reduction of PSMA-TV ≤ 10.7% were identified as independent predictors of shorter PSA-PFS (p = 0.022 and p = 0.043, respectively). For OS, an interim PSMA-TV > 310.3 mL remained an independent prognostic factor both in the entire cohort (p < 0.001) and in the subgroup without early PSA progression (p = 0.002). While baseline SUVmean values were associated with PSA-PFS, no significant association with OS was observed.

[CONCLUSION] In bone-dominant mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA, ΔPSMA-TV ≤ 10.7% and the presence of new lesions were independent predictors of PSA-PFS, while interim bone tumor volume was significantly associated with OS. These findings highlight the clinical relevance of bone-specific volumetric parameters, which may serve as a potential alternative to whole-body tumor assessments by providing more practical and targeted prognostic insights in this patient population.